The alarmingly high lung cancer mortality rate is due mostly to the lack of effective screening protocols for the general public that can detect and diagnose the condition at early and asymptomatic stages. Current radiological examinations, including CT, MRI, and PET, can detect lesions in the lungs;however, their extremely high costs coupled with their unproven efficacies as screening tools have prevented their use in annual screening protocols for the general public. Analyses of blood samples may be a practical and acceptable resource for advancements in lung cancer screening that can advise patients with suspicious readings to seek immediate further radiological tests. In the era of genomics and proteomics, cancer metabolomics collectively evaluate the biological statuses of global metabolite alterations related to malignancy development and progression. Metabolomic profiles measured from cancerous tissues have shown better sensitivity in assessing patient clinical conditions than current histopathology. The aim of the proposed project is to establish lung cancer specific blood serum metabolomic profiles with enough sensitivity and specificity to indicate the necessity for further radiological tests. In this preliminary and exploratory study, we will analyze paired tissue and serum specimens from the same lung cancer patients by using a magnetic resonance spectroscopy method that we developed for intact specimen analyses, search and discover lung cancer tissue metabolomic profiles in connection with tissue pathologies, apply the parameters of these metabolomic profiles obtained from tissue to their corresponding serum spectroscopic data, and test these calculated serum profiles for their ability to identify and group cancer patients. The project is designed to test the hypothesis that serum metabolomic profiles calculated from tissue metabolomic profiles and corrected by quantitative tissue pathologies may have clinical applicability as an early lung cancer screening test for the general public prior to the development of disease symptoms. The specific aims of the project are: 1) To establish serum metabolomic profiles according to tissue metabolomic profiles measured from the same patients for SCC and adenocarcinoma;and 2) to evaluate the sensitivity and specificity of the established serum metabolite profiles for detection and categorization of lung cancers from these patients, and assess and evaluate the clinical utility of the researched lung cancer serum metabolomic marker for screening, using a model from the NCI's Cancer Intervention and Surveillance Modeling Network (CISNET). PUBLIC HEALTH RELEVANCE: This is an exploratory study of paired tissue and serum samples from various lung cancer patients. If successful, annual screening of serum metabolomic profiles established through the initiatives of this project will direct patients with suspicious serum profiles to advanced and expensive radiological tests to detect lung cancers at early and asymptomatic stages, and in turn increase overall patient survival rates and change the paradigm of current oncological clinics.